Abstract:

An endoluminal prosthesis is provided for use in the treatment of a
dilation in a body vessel. This dilation might be an abdominal aortic
aneurysm or a dilation in a blood vessel wall following a balloon
angioplasty procedure. The prosthesis comprises a radially expandable
tubular member and a covering provided on the outer surface of the
tubular member. The covering comprises first and second layers of
material. The first layer comprises an agent that promotes swelling of
the covering on exposure of the covering to contact with body fluid, such
as blood. The second layer comprises space-filling material. When the
prosthesis is delivered into the body vessel the tubular member can
automatically expand or be expanded radially. The covering will also
swell on the tubular member. This expansion and swelling forces the
exterior of the swollen covering into intimate sealing contact with the
surrounding inner wall of the vessel. When used in the treatment of an
aneurysm this can provide significant advantages in eliminating or
reducing primary endoleak.

Claims:

1-59. (canceled)

60. An endoluminal prosthesis for use in the treatment of a dilation in a
surrounding body vessel, the prosthesis comprising:a radially expandible
tubular member having a proximal end, a distal end, an inner lumen, an
outer surface and a circumference; anda covering provided on the outer
surface of the tubular member at least in the region of the proximal and
distal ends, the covering comprising first and second layers of material
which are interleaved and extend generally spirally around the outer
surface of the tubular member, the first layer comprising an agent that
promotes swelling of the covering on exposure of the covering to contact
with body fluid and the second layer comprising a space-filling material,
the covering having the ability to swell in volume to varying degrees
around the circumference of the tubular member;wherein the tubular member
and the covering are constructed and arranged so that, on delivery of the
prosthesis into the surrounding body vessel, the tubular member will
expand radially and the covering will swell in volume on the tubular
member, said expansion and swelling forcing the exterior of the swollen
covering to be pressed into any surface irregularities in the inner wall
of the surrounding body vessel so as to make intimate sealing contact
with the inner wall.

61. A prosthesis as claimed in claim 60, wherein the space-filling
material is generally sponge-like.

62. A prosthesis as claimed in claim 60, wherein the space-filling
material comprises collagen or the like.

63. A prosthesis as claimed in claim 60, wherein the covering is arranged
to conform to the contours of the wall of the vessel at the area of
contact therebetween following delivery of the prosthesis so as to seal
between the swollen covering and the vessel wall.

64. A prosthesis as claimed in claim 63, wherein the seal is to reduce at
least primary endoleak between the delivered prosthesis and the vessel.

65. A prosthesis as claimed in claim 60, wherein the agent is arranged to
swell due to hydrolysis.

66. A prosthesis as claimed in claim 60, wherein the covering includes
thrombogenic material to promote haemostasis in the dilation.

67. A prosthesis as claimed in claim 60, wherein the agent includes an
active agent and that active agent comprises one or more of the
following:hyaluronan, chondroitin sulphates, dermatan and its sulphates,
keratin and its sulphates, and heparin.

68. A prosthesis as claimed in claim 60, wherein the tubular member has a
longitudinal central axis and, relative to that axis, the covering has a
radial thickness of x mm prior to swelling of the covering and a radial
thickness of at least 2x mm following swelling of the covering.

69. A prosthesis as claimed in claim 60, wherein the agent is arranged to
cause the covering to swell on exposure of the covering to contact with
body fluid on delivery of the prosthesis into the vessel from a
prosthesis delivery system.

70. A prosthesis as claimed in claim 60, wherein, when the dilation is an
aneurysm, the covering is arranged to expand outwardly into sealing
contact with the inner surface of the vessel around the aneurysm so as to
isolate the sac of the aneurysm from blood flow along the vessel through
the inner lumen of the expanded tubular member.

71. A prosthesis as claimed in claim 60, wherein the prosthesis is an
aortic aneurysm treatment device.

72. A prosthesis delivery system, comprising the prosthesis of claim 60
and a delivery instrument, wherein the delivery instrument includes a
sheath which is arranged substantially to cover the prosthesis as the
prosthesis is being endolumenally delivered to a target site and
substantially to shield the covering of the prosthesis from contact with
body fluid, the sheath and the prosthesis being relatively movable so as
to enable the prosthesis to be deployed from within the sheath at the
target site to expose the covering of the prosthesis to contact with body
fluid.

73. A method of manufacturing an endoluminal prosthesis,
comprising:providing a substantially fluid impermeable and expandible
tubular member having a proximal end, a distal end, an inner lumen, an
outer surface and a circumference; andapplying a covering, comprising
first and second layers of material, to the outer surface of the tubular
member by simultaneously winding first and second sheets of material
around the tubular member to form the first and second layers
respectively and to produce a covering that comprises the two sheets
interleaved together in a generally spiral arrangement;wherein the first
layer comprises an agent to promote swelling of the covering so as to
cause the covering to swell outwardly on the tubular member on delivery
of the prosthesis into a surrounding body vessel and the second layer
comprising a space-filling material, wherein the tubular member and
covering are constructed and arranged so that, on delivery of the
prosthesis into the surrounding body vessel, the tubular member will
expand radially and the covering will swell in volume on the tubular
member so as to press the exterior of the swollen covering into any
surface irregularities in the inner wall of the surrounding body vessel
so as to make intimate sealing contact with the inner wall.

74. A method as claimed in claim 73, wherein, in the final prosthesis, the
second layer forms the outermost layer of the covering.

75. A method of treating a dilation in a body vessel, the method
comprising the steps of:implanting endovascularly the prosthesis of claim
60;positioning the prosthesis at the site of the dilation to be treated;
andexposing the prosthesis to full contact with body fluid at said site,
the full contact exposure of the agent to said body fluid causing the
covering to swell in size to press the exterior of the swollen covering
into any surface irregularities in the surrounding inner wall of the
vessel so as to make intimate sealing contact therewith.

76. A method as claimed in claim 75, wherein the step of exposing the
prosthesis to full contact with body fluid involves the removal of the
prosthesis from a constraining sheath which sheath, when the prosthesis
is constrained therein, substantially prevents contact between the body
fluid and the covering, wherein the tubular member is self-expandable
and, upon the removal of the constraining sheath, the tubular member
self-expands in diameter, the covering swells so as independently to
expand in volume, thereby pressing the outer surface of the swollen
covering into said intimate sealing contact with the surrounding inner
wall of the vessel, and, upon pressing of the outer surface of the
swollen covering into said intimate sealing contact with the surrounding
inner wall of the vessel, any thrombogenic material and/or drug present
in the covering is pressed into any surface irregularities in the inner
wall of the vessel.

77. A method as claimed in claim 76, wherein, upon contact between the
swollen covering and the inner wall of the vessel at the site of the
dilation, any thrombogenic material present in the covering will promote
clotting of the blood so as further to aid sealing between the prosthesis
and the dilation.

78. A method as claimed in claim 75, wherein the dilation is an aneurysm
and, upon contact between the swollen covering and the inner wall of the
vessel at the site of the aneurysm, any blood in the sac of the aneurysm
is cut-off, from blood flowing along the blood vessel through the inner
lumen of the tubular member of the prosthesis, by the intimate sealing
contact between the exterior of the swollen covering and the surrounding
inner wall of the vessel.

79. A method as claimed in claim 78, wherein the expansion of the
prosthesis into contact with the inner wall of the vessel and the
subsequent clotting of blood associated with that expansion acts to
prevent primary endoleak.

Description:

[0001]This invention relates to medical devices, particularly, but not
exclusively, to endoluminal prostheses for use in the treatment of
dilations such as abdominal aortic aneurysms. The prostheses may find
more general application, for example being used in the manner of stents
following dilation of a vessel as a result of a balloon angioplasty
procedure.

[0002]An abdominal aortic aneurysm (AAA) is a localised weakening of the
walls of the aorta, which causes the aorta to expand or balloon. If this
is left untreated the aneurysm can burst with fatal consequences.

[0003]An established treatment procedure is to open up the patient's
abdomen, open the aneurysm by cutting into it and then to stitch in a
graft, such as a Dacron (Trade Mark) tube, to replace the damaged section
of aorta. More specifically, for repair of an AAA, a tube, or Y-shaped
trouser graft, is commonly sewn in to the aorta during an open operation.
This operation necessitates a mid-line abdominal incision, from the
xiphisternum to the pubis, with exposure of the retro-peritoneal AAA.
After clamping of vessels above and below the aneurysm, the sac would be
opened and the graft inlaid. A proximal anastamosis would be fashioned,
to provide a blood-tight seal, with a similar procedure done distally,
either at the lowermost aorta, or in to the iliac vessels. The patient,
post-procedure, would tend to go to the Intensive Therapy Unit for one to
two days and then to stay on a ward for a further 10-14 days. Complete
recovery would often take 3-6 months.

[0004]Because the surgeon has good access he/she can fix the opposite ends
of the graft to the vessels in a fluid-tight manner. However, the highly
invasive nature of open surgery of this sort, together with its long
patient total recovery times, is undesirable.

[0005]There has been a move over the last 4-5 years to conducting this
procedure less invasively, by using the endoluminal route to repair AAA.
Devices exist that allow endoluminal graft placement from the region of
the femoral artery which, although usually exposed, can be punctured
percutaneously in selected cases. Usually, modular grafts are then
delivered in retrograde fashion, to be sited across the aneurysmal sac,
with the proximal part of the graft located in the aneurysm neck. The
graft, bonded to an underlying metal stent is then deployed from within a
delivery sheath, under fluoroscopic control. Once the stent is in place
an angioplasty balloon catheter positioned internally of it can be
expanded radially outwardly so as to expand the prosthesis into contact
with the inner lumen of the aorta. More recently, memory-shaped materials
such as Nitinol have been used for the stent, which materials have a
memory and spring out to their original shape upon deployment from the
delivery instrument, thereby avoiding the need actively to expand the
stent using a balloon catheter. Such self-expanding devices are commonly
provided on their opposite ends with a series of hooks which penetrate
into the wall of the aorta to hold the device in place. To try to achieve
a good seal between the graft and the internal diameter of the aortic
neck (of the aneurysm) the graft is usually `oversized`. For example, a
34 mm diameter graft might be used to fit a 30 mm diameter neck. Once
deployed, the distal end(s) are sited and the femoral wound closed.
Checks are made continuously to make sure the graft is sited
appropriately. If all has gone well, the endoluminal approach to repair
of AAA means a far lesser `assault` on the patient; meaning no use of
Intensive Therapy Unit facilities, a short hospital stay of 3-4 days
only, with complete recovery in perhaps 3-6 weeks (to allow for the groin
wounds to heal). One disadvantage, however, is the continual radiological
follow-up the patients must undergo. The procedure, if it goes well, is
cost effective.

[0006]A persistent problem with the less invasive endoluminal procedures
is poor sealing between the prosthesis and the patient's aorta at its
opposite ends, particularly at the proximal end (i.e. the upstream end as
regards blood flow, which end is most proximal to the heart). If there is
not good sealing between the prosthesis and the aortic or iliac vessel
walls blood can leak into the sac of the aneurysm, causing the aneurysm
to keep growing with the risk of eventual fatal rupture. This leakage is
known generally as "endoleak", or more specifically "primary endoleak".
It is thought that the incidence of endoleak in endolumenal AAA graft
placement procedures is often as high as 40%. Prevention is through
careful graft `oversizing`, correct assessment of aortic wall anatomy and
correct graft placement. Treatment is by further covered stent placement
(usually balloon-expandable stents) across the neck portion of graft
(aorta), or by waiting to see if the leak will self-close (thrombose).
Additional graft placement(s), and additional admissions and use of
catheters, etc. significantly increases costs, making the whole procedure
cost ineffective.

[0007]Primary endoleak occurs due to the poor fit of an aortic graft in an
aorta. By way of explanation FIG. 1 shows, in axial cross-section, the
aorta 100 of a young and/or healthy individual. As can be seen, the
cross-sectional shape of the aorta is circular. In addition to being
cylindrical, the inner wall 101 of the aorta 100 is also fairly soft.
This makes it easy for the external surface of a cylindrical graft 102 to
form a snug fit with the inner wall 101, as shown. Particularly if the
graft 102 is a self-expanding graft, made of a memory-shape material such
as Nitinol, and is oversized, it will be appreciated that the external
cylindrical surface of the graft 102 will be biased into firm and
effective sealing contact with the inner wall 101 of the aorta, as
denoted by the large arrow in the drawing.

[0008]FIG. 2 shows, in longitudinal cross-section, a Y-shaped trouser
graft 102 placed in the aorta 100, with its Y-shaped legs placed in the
iliac vessels 104. The main cylindrical body of the graft 102 is shown
positioned across the sac 104 of an abdominal aortic aneurysm 103. By
achieving a good fit at the opposite ends of the graft 102 against the
inner walls of the aorta 100 and iliac vessels 105 a good seal can be
achieved at both ends of the graft 102. As a result, the blood flow along
the aorta and iliac vessels is isolated from the blood in the sac 104 of
the aneurysm 103 and primary endoleak is avoided.

[0009]In contrast, the aorta of an elderly and/or unhealthy individual is
often neither generally cylindrical nor soft. The views shown in FIGS. 3
and 4 are generally similar to those shown in FIGS. 1 and 2 respectively,
except that the aorta 110 pictured in FIGS. 3 and 4 is abnormal, having
an irregular inner wall 111. Although the outer wall 112 of the aorta 110
is generally cylindrical, the inner wall 111 is commonly a mixture of
heavy deposits of hard calcium, in conjunction with soft regions of
fatty, cholesterol-rich deposit. The abnormal, non-cylindrical inner wall
111 presented to the external surface of the graft 113 is thus very
difficult for the graft 113 to seal against. Not only is the graft 113
distorted by the abnormal, non-cylindrical nature of the inner wall 111
of the aorta 110, but the graft 113 is unable to form good sealing
contact with the inner wall 111 around its full circumference. Although
the gaps between the exterior of the graft 113 and the inner wall 111 of
the aorta 110 shown in FIG. 3 have been greatly exaggerated for reasons
of clarity, it can be seen that fissures present in the inner wall 111
lead to gaps 114 between the graft 113 and the inner wall 111. As is
shown schematically in FIG. 4, these gaps 114 form possible sites for
endoleak between the exterior of the graft 113 and the inner wall 111 of
the aorta 110. In FIG. 4 arrow 115 shows, schematically, a proximal route
for primary endoleak. Arrow 116 shows a distal route for primary
endoleak.

[0010]There is thus a need for an improved endoluminal prosthesis for use
in the treatment of dilations including an improved endoluminal aortic
aneurysm prosthesis to reduce the incidence of primary endoleak.

[0011]US patent application publication number US 2003/0074058 (published
17 Apr. 2003) discloses a tubular prosthesis in which the prosthesis has
an inner tube and an outer tube, which tubes may be sealed together at
their ends. The inner tube is impervious and the outer tube has at least
a pervious portion. An occluding fluid is, in use, conveyed through a
fluid conduit into a pocket between the inner and outer members so as to
cause portions of the outer member to expand and to seal against the wall
of a blood vessel to prevent Type I endoleaks.

[0012]International patent publication number WO 03/003945 (published 16
Jan. 2003) discloses an implant for use in the treatment of aortic
aneurysms. The implant comprises a graft having a hem defining an
interior space. Enclosed within this space is an absorbent cord. This
cord expands as it comes into contact with body fluids. The expansion due
to the absorbed fluids forms a seal closely following the irregular shape
of the body lumen and improves fixation at the junction of the body lumen
and the implant.

[0013]The present invention provides an endoluminal prosthesis.

[0014]In a first aspect of the present invention this endoluminal
prosthesis can be used in the treatment of a dilation in a body vessel,
such as the aorta. The prosthesis may comprise a tubular member that is
radially expandable and which has proximal and distal ends, as well as an
inner lumen and an outer surface. This tubular member may also be
provided on its outer surface, at least in the region of its proximal and
distal ends, with a covering. This covering may comprise first and second
layers of material. The first layer may comprise an agent that promotes
swelling of the covering on exposure of the covering to contact with body
fluid. The second layer may comprise a space-filling material. The
prosthesis may be configured so that, when delivered into the body
vessel, the tubular member can self-expand or be expanded radially, with
the covering swelling on the tubular member. The intention is for this
expansion and swelling to force the exterior of the swollen covering into
intimate sealing contact with the surrounding inner wall of the vessel.
Where the dilation is an aneurysm, and the vessel is a blood vessel and
the body fluid is blood, it is envisaged that primary endoleak will be
substantially or completely avoided.

[0015]The space-filling material may be generally sponge-like, for example
comprising collagen, gelatin or the like. It may also be advantageous for
the space-filling material to be loaded with a drug or medicament, which
might elute from the prosthesis following prosthesis delivery.

[0016]Instead of simply being provided in the region of the proximal and
distal ends of the tubular member the covering may extend along
substantially the complete length of the outer surface of the tubular
member.

[0017]According to a second aspect of the present invention the
endoluminal prosthesis might be used for the treatment of a body vessel
dilation such as an aneurysm, for example an abdominal aortic aneurysm.
In this situation the prosthesis might once again comprise a radially
expandable tubular member, having proximal and distal ends in a lumen and
an outer surface, and a covering provided on the outer surface of that
tubular member at least in the region of the proximal and distal ends.
The covering may comprise both a thrombogenic material and an agent that
promotes swelling of the covering. This agent may be arranged to cause
the covering to swell in size on exposure of the covering to contact with
body fluid, for example blood. On delivery of this prosthesis into the
vessel it is envisaged that the combined effect of the radial expansion
of the tubular member and the swelling of the covering on the tubular
member may cause the covering to expand outwardly into sealing contact
with an inner wall of the vessel so as to reduce endoleak between the
delivered and expanded prosthesis and the vessel.

[0018]The prostheses of both of the above aspects of the present invention
may also include one or more of the following attributes. For example,
the tubular member, when expanded by generally cylindrical in shape,
having an outwardly facing generally cylindrical surface on which the
covering may be provided.

[0019]The covering may be arranged to conform to the contours of the wall
of the vessel at the area of contact therebetween following delivery of
the prosthesis. An effect of this would be to seal between the swollen
covering and the vessel wall, and in the case of treatment of an AAA to
reduce at least primary endoleak between the delivered prosthesis and the
vessel.

[0020]In the hereinafter described and illustrated embodiments of
endoluminal prosthesis in accordance with the present invention, the
covering has an initial radial thickness prior to contact with the fluid
and the swelling of the covering causes the covering to increase in
radial thickness.

[0021]The agent may be arranged to swell due to hydrolysis.

[0022]The outer surface of the tubular member, for example a stent or
graft, may be completely covered by the covering, or may simply be
covered at the proximal and distal ends of the tubular member.

[0023]The thrombogenic material of the covering is, in the illustrated
embodiments, arranged to promote haemostasis between the layers of the
device itself located in the aneurysm, and is advantageously collagen or
collagen sponge.

[0024]A preferred construction for the covering is to have the first layer
of the covering comprise the agent that promotes swelling of the covering
and the second layer comprise a thrombogenic material. The second layer
advantageously comprises the outermost of the two layers. Furthermore,
the first and second layers are preferably interleaved and extend
generally spirally around the outer surface of the tubular member.

[0025]The covering advantageously takes the form of a tubular collar or
collars around the tubular member. Where the tubular member has a
longitudinal central axis, relative to that axis the radial thickness of
the covering may, for example, be between 0.5 and 1 mm. Furthermore,
relative to that axis, where the covering has a radial thickness of x mm
prior to swelling of the covering it has a radial thickness of at least
2x mm (preferably about 5x) following swelling of the covering.

[0026]The tubular member may need to be expanded, in use, by a balloon
catheter or is, advantageously, self-expanding. In the latter case, the
tubular member advantageously comprises a memory metal such as Nitinol.

[0027]The agent in the covering is advantageously arranged to cause the
covering to swell on exposure of the covering on contact with fluid, for
example blood, on delivery of the prosthesis into the vessel from a
prosthesis delivery system.

[0028]In use, the covering is arranged to expand outwardly into sealing
contact with the inner surface of the vessel on both "sides" of the
aneurysm so as to isolate the sac of the aneurysm from blood flowing
along the vessel through the inner lumen of the expanded tubular member.
It is preferred for the covering not to expand outwardly into sealing
contact with the wall of the sac of the aneurysm, i.e. it is desirable
for sealing contact to be established on either side of the sac of the
aneurysm but not within the volume of the sac of the aneurysm itself.

[0029]The prosthesis is thought to be particularly applicable for the
treatment of aortic aneurysms, and for the prevention of primary
endoleaks. Alternatively or additionally the prosthesis may be used for
treating aneurysms elsewhere, for example in the iliac or femoral
arteries.

[0030]According to a third aspect of the present invention there is
provided the prosthesis of either of the above first and second aspects
of the present invention in combination with a delivery instrument. This
delivery instrument may include a sheath which is arranged substantially
to cover the prosthesis as the prosthesis is being endolumenally
delivered to a target site and substantially to shield the covering of
the prosthesis from contact with blood. The sheath and the prosthesis may
be relatively movable so as to enable the prosthesis to be deployed from
within the sheath at the target site to expose the covering of the
prosthesis to contact with blood.

[0031]In a preferred arrangement the tubular member of the prosthesis is
arranged to be mechanically expanded (either through the use of a
separate tool such as a balloon catheter or through self-expansion) upon
removal of the prosthesis from the sheath, and the agent is arranged to
cause the covering to expand outwardly relative to the expanded tubular
member. The expansion of both the tubular member and the covering
combined, in use, to cause the exterior of the covering to be pressed
into firm sealing contact with the inner lumen of the vessel at the
target site, thereby contributing to reducing endoleak.

[0032]Where the inner lumen of the vessel at the target site is
irregularly contoured, the exterior of the expanded covering is
advantageously arranged to follow the irregular contours so as to effect
the firm sealing contact with the inner lumen of the vessel.

[0033]According to a fourth aspect of the present invention there is
provided a method of manufacturing an endoluminal prosthesis, comprising
providing a substantially fluid impermeable and expandible tubular member
having a proximal end, a distal end, an inner lumen and an outer surface
and applying a covering to the outer surface of the tubular member. This
covering may comprise both a thrombogenic material and an agent to
promote swelling of the covering, the agent being arranged to cause the
covering to swell outwardly on the tubular member towards the inner lumen
of a vessel on delivery of the prosthesis into the vessel. Alternatively
or additionally the covering may comprise first and second layers of
material, with the first layer comprising the above mentioned agent and
the second layer comprising a space-filling material.

[0034]In a preferred arrangement the covering is applied to the tubular
member by winding, around the tubular member, a first sheet comprising
the agent and a second sheet containing the thrombogenic material.
Advantageously, in the final prosthesis the second sheet forms the
outermost layer of the covering.

[0035]In this arrangement the first and second sheets are preferably
simultaneously wound around the tubular member so as to produce a
covering that comprises the two sheets interleaved together in a
generally spiral arrangement.

[0036]According to a fifth aspect of the present invention there is
provided a method of treating a dilation in a blood vessel. The method
may comprise the steps of:

[0037]implanting endovascularly the prosthesis of the above first or
second aspects of the present invention;

[0038]positioning the prosthesis at the site of the dilation to be
treated; and

[0039]exposing the prosthesis to full contact with blood at said site, the
full contact exposure of the agent to said blood causing the covering to
swell in size to press the exterior of the swollen covering into sealing
contact with the inner surface of the vessel.

[0040]In a preferred procedure the step of exposing the prosthesis to full
contact with blood involves the removal of the prosthesis from a
constraining sheath which sheath, when the prosthesis is constrained
therein, substantially prevents contact between the blood and the
covering.

[0041]Where the tubular member is self-expanding, upon the removal of the
constraining sheath the tubular member self-expands in diameter and the
covering independently expands in volume, the combined effect of these
two expansions leading to the outer surface of the covering being pressed
into firm sealing contact with the inner surface of the vessel at the
site of the dilation, with the thrombogenic material of the covering
being pressed into any surface irregularities in the inner surface of the
vessel.

[0042]Advantageously, upon contact between the covering and the inner
surface of a vessel at the site of the dilation, the thrombogenic
material promotes clotting of the blood further to aid sealing between
the prosthesis and the aneurysm.

[0043]Upon contact between the covering and the inner surface of the
vessel at the site of an aneurysm, the covering is preferably only in
contact with the inner surface of the vessel on either side of the
aneurysm. In this way, some of the volume of the sac of the aneurysm is
simply isolated rather than being closed, and any blood present in the
sac of the aneurysm is cut off from blood flowing along the vessel
through the inner lumen of the tubular member of the prosthesis.

[0044]As mentioned above, when positioned at the site of the aneurysm, the
expanded prosthesis preferably bridges across the aneurysm so as to seal
against the inner surface of the blood vessel on both sides of the
aneurysm, but not within the aneurysm itself. Clotting of the blood
within the aneurysm, associated with expansion of the prosthesis into
firm sealing contact with the inner surface of the vessel, advantageously
prevents primary endoleaks.

[0045]In use, clotting of blood at the proximal end of the tubular member
promotes the ingrowth of cells and the incorporation of the proximal end
of the tubular member into the vessel.

[0046]Embodiments of apparatus in accordance with the present invention
will now be described, by way of example only, with reference to the
accompanying drawings, in which:

[0047]FIG. 1 is an axial cross-sectional view, across the line I-I in FIG.
2, of a prior art graft positioned within the aorta of a young and/or
healthy individual;

[0048]FIG. 2 is a schematical longitudinal side elevation of the prior art
graft of FIG. 1 (to a reduced scale) shown positioned across an abdominal
aortic aneurysm;

[0049]FIG. 3 is a view similar to FIG. 1, but shows a prior art graft
positioned in an abnormal aneurysmal aorta of an unhealthy and/or elderly
individual and is sectioned along the line III-III in FIG. 4;

[0050]FIG. 4 is a view similar to FIG. 2, but showing the graft of FIG. 3
(to a reduced scale) placed across an aortic aneurysm with both proximal
and distal endoleak routes identified;

[0052]FIG. 6A shows, in side elevation, a tubular member of an embodiment
of endoluminal prosthesis in accordance with the present invention;

[0053]FIG. 6B shows the tubular member of FIG. 6A provided on its outer
surface with a covering;

[0054]FIG. 6C shows the prosthesis of FIG. 6B with its covering hydrated
and expanded;

[0055]FIG. 6D shows a variant of the prosthesis of FIG. 6B, in which the
covering is provided only at the proximal end of the tubular member;

[0056]FIG. 6E shows a second variant of the prosthesis of FIG. 6B, in
which the covering is provided at both the proximal and distal ends of
the tubular member;

[0057]FIG. 6F shows a third variant of the prosthesis of FIG. 6B, in which
the covering comprises a single layer or sheet of substantially
homogenous construction;

[0058]FIG. 6G shows a fourth variant of the prosthesis of FIG. 6B, in
which the covering comprises a multi-layered arrangement of the
covering's layers;

[0059]FIGS. 7A-7D illustrate a sequence of steps in an exemplary method of
manufacturing a prosthesis;

[0060]FIG. 8A shows, in schematic form, an initial stage in the placement
of the prosthesis of FIG. 6B, showing the prosthesis crimped down and
prevented from radial expansion by a constraining sheath, whilst located
in the aneurysm region of an aorta; and

[0061]FIG. 8B shows a stage subsequent to that illustrated in FIG. 8A, in
which the constraining sheath has been removed and in which the tubular
member has expanded, as has the covering provided on the tubular member,
to force the covering strongly against the inner lumen of the aorta.

[0062]So as to make FIG. 8B more meaningful in due course, FIG. 5 is a
schematic drawing (not to scale) of an aorta 1, with arrow 2 pointing in
the direction of heart (not shown), against the flow of blood from the
heart, and arrows 3 showing the direction of blood flow along the iliac
vessels to the legs. The aorta 1 is shown having an aneurysm 4 formed
therein. Positioned within the aneurysm 4 is a Dacron (Trade
Mark)-covered prior art metal stent 5 provided at its proximal end 6 with
hooks 8 engaging the inner lumen 9 of the aorta 1. As described in the
above introduction to the specification, if the Dacron (Trade
Mark)-covered metal stent 5 (which may or may not be self-expanding) does
not fully engage the inner lumen 9 of the aorta 1 at the ends 6, 7 of the
stent 5 (particularly at the proximal end 6 due to the direction of blood
flow from the heart) leakage of blood into the sac 10 of the aneurysm 4
can occur, preventing clotting of blood in the sac and allowing the
aneurysm to continue to grow in size, risking fatal rupture.

[0063]FIGS. 6A and 6B are two illustrations showing a first endoluminal
prosthesis in accordance with the present invention being built up. The
illustrations are shown as a series, and the components exaggerated in
size, for reason of clarity.

[0064]FIG. 6A is a tubular member 11 having a proximal end 12, a distal
end 13, an inner lumen 14 and an outer surface 15. Provided at the
proximal end 12 are a series of optional hooks 17 for engaging the inner
lumen of a blood vessel, such as an aorta. The tubular member comprises a
metal stent (not visible) in a fluid impermeable covering 16 as is
conventional. The metal stent may advantageously be made of Nitinol so as
to be self-expanding from a collapsed configuration upon delivery from a
constraining sheath, but need not be self-expanding. As is also
conventional, the covering 16 may comprise a sheet of Dacron (Trade Mark)
or similar material fixed to the metal stent usually by a series of
stitches (not shown). Although in the illustrated embodiment the covering
16 is positioned externally of the metal stent, this need not be
so--their positions could be reversed.

[0065]The construction of the tubular member 11 shown in FIG. 6A is, thus
far, conventional. The tubular member 11 is shown in its expanded
configuration. As is conventional, in order to be delivered
endolumenally, the member has to be capable of being collapsed down in
order to reduce its overall diameter to one rendering it capable of
endolumenal delivery.

[0066]FIG. 6B shows the tubular member 11 of FIG. 6A additionally provided
on its outer surface with a covering 22 to form a prosthesis 23. In the
illustrated embodiment the covering 22 comprises a first layer or sheet
20 comprising an agent, and a second layer or sheet 21 comprising a
thrombogenic material and/or space-filling material and not containing
any of the agent. The first layer 20 extends once around the outer
surface of the tubular member 11. The second layer 21 extends once around
the first layer 20, so that the tubular member 11, the first layer 20 and
the second layer 21 form three concentric rings.

[0067]The active ingredient in the agent might be one or more of the
agents discussed below, but the preferred active agent is hyaluronic
acid. Any thrombogenic material may comprise one or more of the materials
discussed below. The preferred material for the second layer or sheet 21
is collagen sponge. The covering 22 provided on the outer surface of the
expanded tubular 11 is shown in FIG. 2B in its non-hydrated, or
unexpanded or unswollen state.

[0068]In contrast, FIG. 6C shows the prosthesis 23 of FIG. 6B in its
hydrated state, such as it would be after exposure to blood. As can be
seen, the hydration of the expansion-promoting agent has led to the first
layer 20 and thus the covering 22 swelling and expanding in volume,
thereby expanding radially outwardly. Space-filling material, such as
collagen, in the second layer 21 will also hydrate too and may expand,
but this is unlikely to be to the same extent as the expansion or
swelling of the first layer 20.

[0069]As will be described below, by positioning the prosthesis 23 in a
lumen and then hydrating the agent, the covering 22 can be caused to
swell outwardly towards the inner lumen of the vessel so as to improve
sealing contact between the exterior of the prosthesis 23 and the inner
lumen of the vessel.

[0070]It should be appreciated that FIGS. 6A-6C, for reasons of clarity,
shows the prosthesis in a non-representative environment, in which it is
not surrounded by a vessel. In normal use, the prosthesis would be
positioned within the lumen of a vessel, prior to hydration of the agent,
so as to provide a surface for the expansion in volume of the agent to
increase the sealing contact with. In addition, FIG. 6C exaggerates the
amount of expansion of the covering 22, brought about by its hydration,
for reasons of clarity.

[0071]FIG. 6D shows a first variant in construction of the prosthesis 23
of FIGS. 6B and 6C. As can be seen, in FIG. 6D the covering 22 is
provided only at the proximal end 12 of the tubular member 11. In
addition the hooks are omitted.

[0072]FIG. 6E shows a second variant. In FIG. 6E the covering 22 is
present at both the proximal and distal ends 12,13 of the tubular member
11 but the central portion of the tubular member is not provided with the
covering 22. When used as a graft for treatment of an AAA, the intention
is that the coverings 22 at the ends should be aligned with the portions
of the blood vessel on either side of the aneurysm sac, with the central
portion of the tubular member being aligned with and bridging across the
sac of the aneurysm.

[0073]Although in FIGS. 6B-6E the covering 22 is shown as being provided
with a plurality of discrete layers or sheets 20,21, one comprising an
agent to promote swelling and the other comprising a thrombogenic
material, the covering 22 may comprise a single layer or sheet of
substantially homogeneous construction, for example in which the
thrombogenic material and the agent are combined together, as shown in
the third variant of prosthesis in FIG. 6F.

[0074]Equally, rather than simply comprising two concentrically arranged
discrete layers or sheets 20, 21 as in FIGS. 6B-6E, the covering 22 might
alternatively comprise a plurality of one or other (or both) types of
layer or sheet. For example, as shown in the fourth variant in FIG. 6G,
the covering 22' comprises a pair of first layers or sheets 20' and a
pair of second layers or sheets 21', arranged in the order: 20', 21' 20',
21', etc. The provision of a plurality of interleaved layers or sheets
21' is thought likely to enhance the thrombogenic effect and thus the
sealing effect. When the prosthesis is deployed, and the plural layers in
the covering are "wetted" in the blood flow, in addition to activating
the agent in the first layers 20' blood may be trapped in the interstices
between the adjacent layers 20', 21'. This blood trapped between the
interleaved layers 20', 21' of the covering 22 will then clots, enhancing
further the sealing ability of the prosthesis.

[0075]There will now be described, in conjunction with the sequence of
FIGS. 7A-7D a sequence of steps in an exemplary method of manufacturing
an endoluminal prosthesis 23 (in accordance with the invention). Where
elements of the prosthesis 23 have a similar function to elements in
embodiments or variants of prosthesis already described, these will be
referenced with the same reference numerals.

[0076]As explained above in connection with FIG. 6A, the underlying
tubular member 11 of the endoluminal prosthesis 23 of the present
invention can have a known construction and shape. Although, for reasons
of simplicity, the endoluminal prosthesis shown in the drawings is a
simple tubular stent or graft, the prosthesis could have any shape or
configuration appropriate to its intended location in the body, for
example, a Y-shaped trouser graft. The novel and inventive aspect of the
prosthesis of the present invention is largely provided by the covering
22 on the outer surface of the tubular member 11.

[0077]Where the agent to promote swelling of the covering and the
thrombogenic material are to be provided in separate sheets or layers, it
is necessary first to manufacture the two different types of layer or
sheet 20, 21.

[0078]The second layer or sheet 21 may comprise a rectangular sheet of
collagen foam, as illustrated in FIG. 7A. Alternatively, one can take a
mixture of available collagen extract (usually presented in an acidic
base), neutralise it and pour it into a mould in which it will set at
room temperature. By regulating the depth of the liquid in the mould one
can control the thickness of the resultant sheet. Once the material has
set, it can be moved from the mould and have moisture removed from it by
lightly compressing it, for example using blotting paper. The resultant
sheet of material can either be a very large sheet, from which the sheet
21 illustrated in FIG. 7A can be cut, or the mould may be appropriately
sized.

[0079]To produce the first layer or sheet 20 one can taken hyaluronic acid
in powdered form, mix it with distilled water, pour it into an
appropriately shaped mould to a desired depth and freeze-dry it so as to
form a flat sheet of material. This sheet 20, which can also either be
cut to size or moulded in the appropriate size, can then be laid on the
second sheet 21, as shown in FIG. 7B. As long as there is no excess water
in the second layer or sheet 21, the placing of the first sheet 20 on the
second sheet 21 should not cause the hyaluronic acid to become hydrated.

[0080]In a preferred arrangement, the longitudinal element of the first
sheet 20 is less than that of the second sheet 21. An uncovered tongue
portion 30 of the second sheet 21 enables the tubular member 11, in its
expanded form and containing a mandrel (not shown) to rigidify it, to be
positioned on the right-hand edge (as drawn) of the tongue 30, in the
manner shown in FIG. 7C. By then rolling the tubular member 11 in the
direction of arrow 31 in FIG. 7C, the two sheets 20, 21 that form the
covering 22 can be wrapped, in a generally spiral fashion, around the
outer surface of the tubular member 11. Apart from the first layer of the
covering 22 that will be exclusively comprised by the tongue portion 30
of the second sheet 21, the first and second sheets 20, 21 will be
interleaved as they spiral around the central longitudinal axis of the
tubular member 11. FIG. 7D shows the arrangement part way through the
wrapping process. If an uncovered tongue (not shown) of the second sheet
21 is also provided at the left hand end of the sheet, when the wrapping
process is finished the end of that tongue may be stuck to the portion of
the second sheet immediately below it to make the covering secure.

[0081]It will, of course, be appreciated that the covering 22 may be
applied to the tubular member 11 in other ways, for example by spraying,
dipping, coating etc. to form one or more layers.

[0082]In order to package the prosthesis ready for use, it is necessary to
remove the mandrel (not shown) from the lumen of the tubular member 11
and to crimp down the prosthesis so as to reduce its outer diameter. The
reduction in outer diameter might typically be from any one of 19.5, 21.5
or 23.5 mm to approximately 6 mm (for the prosthesis to be constrained in
an 18 French inner diameter delivery system sheath) or from any one of
25.5, 28, 30.5, 32 and 34 mm to 6.66 mm (to be constrained in an 20
French inner diameter delivery system sheath. The smaller the diametral
dimension that can be achieved on crimping down the better, because
smaller prosthesis may be more readily delivered and/or delivered via
smaller vessels. The prosthesis would be crimped down onto a conventional
delivery system in the manner of a conventional non-coated endoluminal
prosthesis, and then vacuum packaged to keep it sterilized and dry. In
its packaged state the crimped down prosthesis is preferably constrained
radially by a constraining delivery system sheath. As will be described
below, upon being released from this constraining sheath the prosthesis
is able to be expanded radially by a balloon catheter (in the case of a
non-self-expanding prosthesis) or will automatically self-expand (in the
case of a self-expanding prosthesis).

[0083]It is anticipated that the prosthesis 23 will have a shelf-life of
very many months (ideally years) if stored appropriately. When the time
comes to use the prosthesis, for example to treat an aortic aneurysm
endolumenally, the initial stages of the procedure will be as with a
prior art uncoated prosthesis.

[0084]In a typical procedure, as shown in FIG. 8A, the crimped down
prosthesis 23, constrained against expansion by a constraining sheath 40,
is fed endolumenally to the site of the aneurysm in a conventional
manner. Using a fluoroscope the surgeon can position the
prosthesis-containing portion of the sheath 40 bridging the aneurysm 41
to be treated. In FIG. 8A the crimped down prosthesis 23, having the
construction of the FIG. 6B prosthesis, is shown in dotted lines.

[0085]As is conventional, it is anticipated that the prosthesis 23 will be
supplied to the surgeon in a range of sizes, from which range to surgeon
may pick the prosthesis with the most appropriate size. Typically the
outer diameter of the unconstrained prosthesis 23 is chosen to be
slightly oversize relative to the vessel (such as an aorta 42) into which
the prosthesis is to be placed. For example, it is anticipated that a
prosthesis 23 with an unconstrained outer diameter of 19.5 mm (measure
across the covering 22 before swelling of the covering) would be suitable
for use in a vessel with an native vessel inner diameter of 16.0-17.5 mm.
In this way, the mechanical expansion of the prosthesis 23 (even before
swelling of the covering 22) can be used to promote good sealing at the
ends of the prosthesis 23, with subsequent swelling of the covering 22
further enhancing sealing. Exemplary sizes are listed below (in
millimetres), with an unconstrained prosthesis outer diameter listed
first, followed by an exemplary matching native vessel inner diameter in
parentheses: 19.5 (16.0-17.5); 21.5 (17.5-19.5); 23.5 (19.5-21.5); 25.5
(21.0-23.5); 28.0 (23.0-25.5); 30.5 (25.0-27.5); 32.0 (26.5-29.5); 34.0
(28.5-31.5).

[0086]The procedure described below is for a self-expanding tubular
member. In addition to constraining the crimped down prosthesis 23
against radial self-expansion, the sheath 40 has the effect of
substantially shielding the prosthesis 23 from contact with blood in the
aorta 42. Consequently, the agent that will promote swelling of the
covering is substantially prevented from being hydrated prematurely.

[0087]Once the surgeon determines that the prosthesis 23 is appropriately
positioned, by then holding the prosthesis 23 in place using a pusher 43
and withdrawing the sheath 40, the sheath 23 is left in position exposed
to blood in the aorta 42. By continuing to hold the prosthesis 23 using
the pusher 43 to resist the strong flow of blood in the aorta 42, in the
case of a self-expanding prosthesis the prosthesis 23 will self-expand as
shown in FIG. 8B. As described above, by using a slightly oversize
prosthesis 23 the mechanical expansion of the tubular member 11 alone may
be sufficient as to bring the outside surface of the non-hydrated
covering 22 into firm contact with the inner lumen of the aorta 42--this
is to be preferred because the hydration of the covering will then be
able to push the covering hard against the wall of the aorta 42. Because
the external profile of the tubular member 11 is general cylindrical, the
mechanical expansion of the tubular member 11 alone may be unable to cope
with small scale discontinuities or deviations, such as fissures or
calcified plaques, in the inner lumen of the wall of the aorta which
depart from a generally circular profile.

[0088]In FIG. 8B the drawing of the prosthesis 23 is split down its centre
for reasons of clarity. To the right-hand side of the centre-line of the
prosthesis the expanded covering 22 is shown as being in contact with the
inner lumen of the aorta at the ends of the prosthesis, but not in the
centre of the prosthesis. The non-constant outside diameter of the
expanded prosthesis is accounted for by differing degrees of expansion of
the covering 22 along the length of the prosthesis. This is shown most
readily in the left-hand half of FIG. 8B. In the left-hand half the
tubular member 11 is shown as being mechanically expanded, through its
self-expansion mechanism, into contact with the narrowest portions of the
inner lumen of the aorta. Where the aneurysm sac was previously, the
outer layer or sheet 21 of the covering 22 is shown (in black) as having
expanded part way into the volume of the aneurysm sac by virtue of the
expansion of the first layer or sheet 20 of the covering 22.

[0089]In order to prevent primary endoleak it is sufficient for the
covering 22 to be in contact with the inner lumen of the aorta at simply
the end or ends of the prosthesis 23, as shown. It is not necessary for
the full volume of the aneurysm sac to be taken up by the expanded
covering 22, so that in the central portion of the sac the covering 22 is
not required to expand to a size equal to the maximum dimension of the
aneurysm sac. Instead, the central portion of the sac is intended to
contain a volume of blood 50 that is cut off from blood 51 flowing along
the aorta through the inner lumen 14 of the tubular member.

[0090]In addition to the mechanical expansion of the tubular member, the
removal of the sheath 40 from the exterior of the prosthesis 23 means
that the prosthesis is no longer substantially shielded from blood. The
effect of blood contacting the covering 22 is to cause the active agent
in the agent that promotes swelling of the covering to hydrate, causing
the covering to swell expand in volume. The expansion in volume causes
the external dimension of the prosthesis to increase beyond that which is
achieved simply by mechanical expansion of the self-expanding tubular
member 11. It is this swelling or expansion which causes the covering to
be squeezed tightly against the inner lumen of the aorta 42 on either
side of the aneurysm. Where the agent and thrombogenic material are
provided in discrete layers or sheets 20,21, it is the thrombogenic
material of the second layer or sheet 21 that is preferably outermost on
the prosthesis. This thrombogenic material is squeezed into contact with
the inner lumen of the aorta at the ends of the prosthesis by virtue of
the combined (i) mechanical radial expansion of the tubular member 11 and
(ii) the expansion of the covering 22 on the tubular member. It is this
combined effect which causes the covering to expand outwardly into
sealing contact with the inner surface of the aorta at the opposite ends
of the aneurysm to reduce endoleak between the delivered and expanded
prosthesis and the aorta.

[0091]It will be appreciated that the expansion of the covering 22 is more
readily able to accommodate discontinuities within the inner lumen of the
aorta than is mechanical expansion of the tubular member, for example
discontinuities caused by atheroma.

[0092]The effect of the expansion of the covering 22 is to improve sealing
between the prosthesis and the inner lumen of the aorta, particularly in
cases where the inner lumen is irregular in shape from plaque and/or
fissured.

[0093]The agent that promotes swelling of the covering is thought likely
to cause the covering to expand outwardly in fewer than 5 minutes,
preferably fewer than a couple of minutes. The timing can be modified
through the use of differing amounts of the active agent, making it
possible to fabricate `fast` and `slow` expanding versions of the
prosthesis. The expansion should advantageously not, however, be so quick
as to prevent the surgeon from repositioning the prosthesis if, on
withdrawal of the constraining sheath 40, the prosthesis is moved out of
position.

[0094]In use, it is envisaged that the prosthesis should extend by a
distance (reference 45) approximately 1-3 cm beyond each end of the
aneurysm, both proximally, at the `neck` of the aneurysm, and distally,
most likely into one or other of the iliac arteries.

[0095]Once the tubular member has mechanically expanded and the covering
has also expanded, the delivery apparatus may be withdrawn. In the case
where the prosthesis is provided with hooks the combined effect of those
hooks and the expansion of the prosthesis against the inner wall of the
aorta should be sufficient as to keep the prosthesis in place, despite
the strong blood flow.

[0096]It is envisaged that the prosthesis will be provided to a surgeon in
a range of different sizes, for example differing in outside diameter by
2 mm steps across the range, and different swelling rates. The surgeon
will thus be able to select a prosthesis of an appropriate size and
deployment speed. In its non-hydrated state, the covering 22 may have a
radial thickness of, for example, 0.5 mm, but when hydrated may have a
radial thickness of approximately 2-3mm (or more). Consequently,
providing a 0.5 mm thick covering around a tubular member, where the
tubular member has an outside diameter of 30 mm in its mechanically
self-expanded state, will cause the non-hydrated prosthesis to have an
outside diameter of approximately 31 mm. Upon hydration of the covering,
however, the outside diameter of the self-expanded prosthesis will be
approximately 34-36 mm, i.e. an increase in diameter of approximately 35
mm.

[0097]Although in the embodiments described to date the tubular member 11
has generally been cylindrical, it may take other shapes, for example
having at least one divergent arm (or even two, to have an inverted-Y
shape) so as to enable the prosthesis to be sited at the distal branching
of the aorta into the iliac arteries.

[0098]Once the prosthesis has been deployed and the agent has caused the
covering to swell and expand outwardly to press the thrombogenic material
against the inner lumen of the aorta (and into any surface irregularities
in the inner lumen of the aorta) on either side of the aneurysm, the
active ingredient in the thrombogenic material, for example collagen,
activates the `clotting cascade`. Clotting of blood external to the
tubular member of the prosthesis further promotes good sealing between
the prosthesis and the inner lumen of the aorta, reducing primary
endoleaks. Generally speaking, after a few weeks, the risk of endoleaks
lessens, because the cells of the inner lumen of the aorta grow on to the
inner lumen of the tubular member of the prosthesis yet further,
assisting sealing and location of the prosthesis. It is anticipated that,
once deployed, blood will over time occupy some of the volume that was
occupied by the expanded expansion-promoting agent, but this blood should
clot very quickly due to the proximity to thrombogenic material. Clotting
at the surface of the thrombogenic material (e.g. collagen) is likely
also to be promoted by localised dehydration of the of the blood layer by
the swelling material with which it is in direct contact. Hence blood
proteins, coagulation factors and platelets for example should all be
concentrated onto and `sucked` onto the thrombogenic material. Any
remaining swelling-promoting agent may, over time, turn to gel and pass
down harmlessly into the sac of the aneurysm.

Preferred Agent to Promote Swelling

[0099]Although the agent to promote swelling is disclosed in the preferred
embodiment as comprising hyaluronic acid originating in powdered form,
the agent can be any significantly or substantially charged polymer
molecule or even monomer which is, or can be, aggregated to form very
high molecular weight complexes. Advantageously, the agent must be (or be
able to rapidly become, for example within a few seconds or at least
minutes) very large in molecular dimensions, ie. >>1 million
molecular weight. Ideally, it should be or be able to rapidly become
large enough to be trapped within or excluded by the pores in the
thrombogenic material (commonly this may be in the range 100 nm to 100
μm in any one dimension). Trapping or exclusion might be through total
aggregate dimensions, very high aspect ratio (fibres with high length to
width) or by having substantial physico-chemical affinity for the second,
trapping element (eg ligand-receptor activity, complementary chemical
binding sites etc.).

[0100]Ideally the agent that promotes swelling is a very large soluble or
insoluble polymer solid. If required, aggregation of a monomeric swelling
element (eg {single, self aggregating, compound or combination of
interacting molecules} drug, small molecule, protein, polysaccharide,
synthetic polymer-precursor) could be envisaged, providing its
aggregation was complete very rapidly after insertion and exposure to
blood or its components.

[0101]Rapid swelling of the first element (ie generation of the molecular
motor function) is ideally by uptake of fluid from surroundings by
osmotic flow, out of the surrounding fluids and tissues to hydrate the
swelling element. This is best driven by a high and controllable fixed
charge density on the polymer or aggregate. Commonly and most simply this
is provided by a number of naturally occurring (or, in time, synthetic)
charged polysaccharides, ideally hyaluronan but also chondroitin
sulphates, dermatan and its sulphates and keratin and its sulphates, all
well known in the field. Other neutral polysaccharides could be used,
particularly if they were modified to carry high fixed charge densities.
The fixed charge density must be sufficient to cause the polymer to swell
rapidly on first exposure to aqueous fluids, and sufficient to be able to
draw this fluid from surrounding biological tissues against their own
hydration gradients. Ideally, this means that the swelling polymer will
rapidly form an expanding gel immediately on exposure to aqueous fluids,
at the same time generating significant mechanical force associated with
that swelling, again ideally focussed on tissue or implant layers
adjacent to the swelling element (ie localised forces, especially between
layers). It is chemically possible to modify almost any polymer to
introduce such high fixed charges, though clearly many will be or will
generate undesired (toxic) effects in the body. Other candidate might be
clinically acceptable polymers (ideally biodegradable), proteins (ideally
self or catalytically/enzyme aggregating, eg amphyphillic peptides,
extracellular matrix proteins, fibrin(ogen)), polynucleic acids, even
(though less likely because of their dominant hydrophobic nature) lipids.
Ideally, swelling needs to be controllable in terms of rate and even
force generated and this would require that the fixed charge density be
controlled and even constant over the average volume of the swelling
element, otherwise swelling and occlusion in any given time frame or
against any given flow pressure could not be guaranteed or predicted.

Thrombogenic Material

[0102]Although in the illustrated embodiment the thrombogenic material
includes collagen foam, other materials may be used to provide a
haemostatic effect. Ideally, the thrombogenic material would be a
clinically acceptable solid polymeric material with controllable pores
(˜100 nm to 100 μm average range diameter though potentially
larger or smaller than this). It should have sufficient material strength
and integrity to retain its shape and structure within its layer
position, against competing forces, fluid shears and especially
compression. It must have a lower inherent swelling pressure (fixed
charge density) than the swelling element. Fibrous extracellular matrix &
structural proteins (collagen, clotting proteins (fibrin, fibronectin)
silks are ideal for this, but synthetic polymers, neutral polysaccharides
(chitin, cellulose, starch) could be used to some extent, particularly
after chemical modifications, as long as they could fulfill the
mechanical requirements. Fibrous or porous solid polymers (random or
non-random) are best, others include granular materials (large particles)
less desirable are small particle granules, emulsions, micro-beads etc.
if used without restraining/enclosing layers.

[0103]The idea has two parallel mechanisms, (i) physical occlusion and
(ii) promotion of haemostasis. Some trapping elements could act using
only one of these, though less effectively and less rapidly. Aggregated,
solid, native collagen is ideal as it is a naturally strong, flexible
material, low swelling potential, clinically acceptable (low antigenicity
etc) yet it promotes rapid platelet aggregation and degranulation, i.e.
initiates the full clotting cascade. Other versions might use immobilised
factors, peptide sequences or enzymes to mimic this activity, e.g. by
initiating platelet aggregation/degranulation and or fibrin aggregation
from fibrinogen (e.g. most simply by provision of active thrombin). Such
mechanisms might also be used with collagen to further enhance, speed up
its role where needed. Significant non-ideal, other candidates for this
might be chemically modified synthetic polymers, aggregated
non-structural (globular) proteins such albumin, immunoglobulins, neutral
polysaccharides such as cellulose, chitin etc), even inorganic backbone
materials, if sufficiently flexible, such as glass (eg soluble phosphate)
fibres, ceramic particles, kaolin, etc. However, many of these are not
mechanically suitable and or would cause significant clinical problems
if/when they were released into the rest of the body, eg generating
tissue toxicity, immune reactions/inflammation, dangerous coagulations
and small vessel constrictions.

[0104]Longer term stabilisation of the interface between the prosthesis
and the vessel with which it is in contact might be accelerated by the
addition of factors such as TGF-β isoforms, for example to the
thrombogenic material, to promote rapid fibrous ingrowth into the newly
formed clot.

Treatment of the Non-Aneurysmal Dilations

[0105]The description and drawings thus far primarily concern the
treatment of aneurysmal dilation and the prevention of primary endoleak.
The prosthesis of the present invention does, however, find uses in the
treatment of non-aneurysmal dilations where the benefits do not relate to
primary endoleak prevention.

[0106]A further use envisaged for the endoluminal prosthesis of the
present invention concerns a balloon angioplasty procedure. In such a
procedure, it is common to use a balloon catheter to dilate a narrowing
in an artery and then to insert a stent into the dilated artery so as to
assist in keeping the artery open. It is also know for such stents to be
a drug or medicament eluting stent, which elute the drug or medicament
over time. Rather than using a prior art stent following a balloon
angioplasty procedure it is envisaged that the endoluminal prosthesis of
the present invention could be used instead. In such a situation, it is
unlikely that the covering on the tubular member of the prosthesis would
comprise thrombogenic material, but it might if the underlying body of
the stent was provided with a fluid impermeable membrane so as to
minimise entry of the thrombogenic material into blood passing through
the lumen of the tubular member. Instead, it is envisaged that the
covering, preferably the second layer of material in the covering, would
comprise a space-filling material such as collagen which is loaded with
drug or medicament. As in the earlier embodiments, the expansion of the
tubular member and the swelling of the covering provided on the outer
surface of the tubular member would have the effect of forcing the
exterior of the swollen covering into intimate contact with the
surrounding inner wall of the vessel at the site of the balloon
angioplasty. The sponge-like nature of the covering, together with the
intimate contact between the covering and the surrounding inner wall of
the vessel, could be used to promote "incorporation" of the prosthesis
into the wall of the vessel. Furthermore, if the covering was provided
with a drug or medicament, the intimate contact between the drug or
medicament-loaded covering and the surrounding inner wall of the vessel
could be used to promote healing between the stent and the vessel wall.

[0107]In other words, the dilation being treated can be as a result of the
surgical expansion of an unwanted constriction, rather than a naturally
occurring unwanted dilation such as an aneurysm.

Potential Attributes

[0108]Attributes foreseen for the endoluminal prosthesis of the present
invention, whether used for the treatment of non-aneurysmal dilations or
not, may include one or more of the following.

[0109]1. To effectively close spaces between the prosthesis and the
surrounding inner wall of the vessel.

[0110]2. To enable outward expansion of the covering away from the tubular
member, to varying degrees.

[0111]3. To enable expansion only once the prosthesis has been delivered
from a surrounding sheath.

[0112]4. To be able to be crimped for containment in a delivery sheath.

[0113]5. To have a reasonable shelf life.

[0114]6. To be easy to manufacture and to readily reproducible.

[0115]7. To be cost efficient.

[0116]8. To be non-toxic and avoid causing significant complications.

[0117]9. To promote further "incorporation" and healing between the
prosthesis and the surrounding vessel walls.

[0118]10. To be applicable to any size of graft or stent available now or
in the future.

[0119]11. To be able to have a desiccated, crimped diameter of
approximately 0.5 mm.

[0120]12. To expand in diameter, on swelling, to greater than 3 mm

[0121]13. To swell in less than two minutes.

[0122]14. To promote thrombis formation between the layers of the
covering.